The Research Center for Clinical Pharmacology and Drug Toxicology consists of clinical pharmacologists in Internal Medicine, Psychiatry and Pediatrics working in close association with a nucleus of investigators (in the Department of Pharmacology) who have a high level of competence in drug metabolism and other biochemical approaches to pharmacology. The scientific resources in the Center will enable the application of the best available techniques and approaches to studies of drugs in man. The multidisciplinary research program of the Center will provide an optimal environment for training investigators in clinical pharmacology. The research program will focus on the metabolism, distribution, and biochemical effects of drugs in man. Within this framework, attention will be given to the delineation of drug interactions, investigation of their mechanism, and the development of clinical techniques which can predict toxicity and drug interaction in patients. In areas such as the prostaglandin precursors and the false neurotransmitters, new approaches to the delivery of active compounds to their sites of action will be investigated. Particular attention will be given to the marked inter-individual differences in plasma levels between individuals and their relevance to efficacy and toxicity. A further aim will be the development of assay techniques which can accurately detect nanogram and picogram amounts of drugs and metabolites in plasma, tissues, and urine of patients. This will involve wider and improved application of techniques such as isotope derivative assay, immunoassay, fluorescence assay, and gas chromatography with a number of detection modes including quantitative application of the multiple ion detector of the mass spectrometer. Studies of metabolism, distribution, transport, binding and biochemical effects of drugs in a variety of species will be carried out in an attempt to provide a rational basis for the prediction of action, interaction, and toxicity in man.